Background: A growing body of observational evidence supports the value of ceftazidime-avibactam (CAZ-AVI) in managing infections caused by carbapenem-resistant Enterobacteriaceae. Methods: We retrospectively analyzed observational data on use and outcomes of CAZ-AVI therapy for infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) strains. Multivariate regression analysis was used to identify variables independently associated with 30-day mortality. Results were adjusted for propensity score for receipt of CAZ-AVI combination regimens versus CAZ-AVI monotherapy. Results: The cohort comprised 577 adults with bloodstream infections (n = 391) or nonbacteremic infections involving mainly the urinary tract, lower respiratory tract, and intra-abdominal structures. All received treatment with CAZ-AVI alone (n = 165) or with ≥1 other active antimicrobials (n = 412). The all-cause mortality rate 30 days after infection onset was 25% (146/577). There was no significant difference in mortality between patients managed with CAZ-AVI alone and those treated with combination regimens (26.1% vs 25.0%, P =. 79). In multivariate analysis, mortality was positively associated with presence at infection onset of septic shock (P =. 002), neutropenia (P <. 001), or an INCREMENT score ≥8 (P =. 01); with lower respiratory tract infection (LRTI) (P =. 04); and with CAZ-AVI dose adjustment for renal function (P =. 01). Mortality was negatively associated with CAZ-AVI administration by prolonged infusion (P =. 006). All associations remained significant after propensity score adjustment. Conclusions: CAZ-AVI is an important option for treating serious KPC-Kp infections, even when used alone. Further study is needed to explore the drug's seemingly more limited efficacy in LRTIs and potential survival benefits of prolonging CAZ-AVI infusions to ≥3 hours.
Ceftazidime-avibactam use for klebsiella pneumoniae carbapenemase-producing k. pneumoniae infections: A retrospective observational multicenter study / M. Tumbarello, F. Raffaelli, M. Giannella, E. Mantengoli, A. Mularoni, M. Venditti, F.G. De Rosa, L. Sarmati, M. Bassetti, G. Brindicci, M. Rossi, R. Luzzati, P.A. Grossi, A. Corona, A. Capone, M. Falcone, C. Mussini, E.M. Trecarichi, A. Cascio, E. Guffanti, A. Russo, G. De Pascale, C. Tascini, I. Gentile, A.R. Losito, L. Bussini, G. Corti, G. Ceccarelli, S. Corcione, M. Compagno, D.R. Giacobbe, A. Saracino, M. Fantoni, S. Antinori, M. Peghin, P. Bonfanti, A. Oliva, A. De Gasperi, G. Tiseo, C. Rovelli, M. Meschiari, N. Shbaklo, T. Spanu, R. Cauda, P. Viale. - In: CLINICAL INFECTIOUS DISEASES. - ISSN 1058-4838. - 73:9(2021 Nov 02), pp. 1664-1676. [10.1093/cid/ciab176]
Ceftazidime-avibactam use for klebsiella pneumoniae carbapenemase-producing k. pneumoniae infections: A retrospective observational multicenter study
S. Antinori;
2021
Abstract
Background: A growing body of observational evidence supports the value of ceftazidime-avibactam (CAZ-AVI) in managing infections caused by carbapenem-resistant Enterobacteriaceae. Methods: We retrospectively analyzed observational data on use and outcomes of CAZ-AVI therapy for infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) strains. Multivariate regression analysis was used to identify variables independently associated with 30-day mortality. Results were adjusted for propensity score for receipt of CAZ-AVI combination regimens versus CAZ-AVI monotherapy. Results: The cohort comprised 577 adults with bloodstream infections (n = 391) or nonbacteremic infections involving mainly the urinary tract, lower respiratory tract, and intra-abdominal structures. All received treatment with CAZ-AVI alone (n = 165) or with ≥1 other active antimicrobials (n = 412). The all-cause mortality rate 30 days after infection onset was 25% (146/577). There was no significant difference in mortality between patients managed with CAZ-AVI alone and those treated with combination regimens (26.1% vs 25.0%, P =. 79). In multivariate analysis, mortality was positively associated with presence at infection onset of septic shock (P =. 002), neutropenia (P <. 001), or an INCREMENT score ≥8 (P =. 01); with lower respiratory tract infection (LRTI) (P =. 04); and with CAZ-AVI dose adjustment for renal function (P =. 01). Mortality was negatively associated with CAZ-AVI administration by prolonged infusion (P =. 006). All associations remained significant after propensity score adjustment. Conclusions: CAZ-AVI is an important option for treating serious KPC-Kp infections, even when used alone. Further study is needed to explore the drug's seemingly more limited efficacy in LRTIs and potential survival benefits of prolonging CAZ-AVI infusions to ≥3 hours.File | Dimensione | Formato | |
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